scholarly journals Neuroinflammation in Primary Open-Angle Glaucoma

2020 ◽  
Vol 9 (10) ◽  
pp. 3172 ◽  
Author(s):  
Stefania Vernazza ◽  
Sara Tirendi ◽  
Anna Maria Bassi ◽  
Carlo Enrico Traverso ◽  
Sergio Claudio Saccà

Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increasing evidence suggests oxidative damage and immune response defects are key factors contributing to glaucoma onset. Indeed, both the failure of the trabecular meshwork tissue in the conventional outflow pathway and the neuroinflammation process, which drives the neurodegeneration, seem to be linked to the age-related over-production of free radicals (i.e., mitochondrial dysfunction) and to oxidative stress-linked immunostimulatory signaling. Several previous studies have described a wide range of oxidative stress-related makers which are found in glaucomatous patients, including low levels of antioxidant defences, dysfunction/activation of glial cells, the activation of the NF-κB pathway and the up-regulation of pro-inflammatory cytokines, and so on. However, the intraocular pressure is still currently the only risk factor modifiable by medication or glaucoma surgery. This present review aims to summarize the multiple cellular processes, which promote different risk factors in glaucoma including aging, oxidative stress, trabecular meshwork defects, glial activation response, neurodegenerative insults, and the altered regulation of immune response.

2013 ◽  
Vol 13 (1) ◽  
pp. 98-107 ◽  
Author(s):  
Maria D Pinazo-Durán ◽  
Vicente Zanón-Moreno ◽  
Jose J García-Medina ◽  
Roberto Gallego-Pinazo

2021 ◽  
Vol 22 (5) ◽  
pp. 2421
Author(s):  
Saray Tabak ◽  
Sofia Schreiber-Avissar ◽  
Elie Beit-Yannai

Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular meshwork (TM) cells, inducing apoptosis of the retinal ganglion cells (RGC), deteriorating the optic nerve head, and leading to blindness. Aqueous humor (AH) outflow resistance and intraocular pressure (IOP) elevation contribute to disease progression. Nevertheless, despite the existence of pharmacological and surgical treatments, there is room for the development of additional treatment approaches. The following review is aimed at investigating the role of different microRNAs (miRNAs) in the expression of genes and proteins involved in the regulation of inflammatory and degenerative processes, focusing on the delicate balance of synthesis and deposition of extracellular matrix (ECM) regulated by chronic oxidative stress in POAG related tissues. The neutralizing activity of a couple of miRNAs was described, suggesting effective downregulation of pro-inflammatory and pro-fibrotic signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), transforming growth factor-beta 2 (TGF-β2), Wnt/β-Catenin, and PI3K/AKT. In addition, with regards to the elevated IOP in many POAG patients due to increased outflow resistance, Collagen type I degradation was stimulated by some miRNAs and prevented ECM deposition in TM cells. Mitochondrial dysfunction as a consequence of oxidative stress was suppressed following exposure to different miRNAs. In contrast, increased oxidative damage by inhibiting the mTOR signaling pathway was described as part of the action of selected miRNAs. Summarizing, specific miRNAs may be promising therapeutic targets for lowering or preventing oxidative stress injury in POAG patients.


2011 ◽  
Vol 36 (8) ◽  
pp. 713-718 ◽  
Author(s):  
Mesut Erdurmuş ◽  
Ramazan Yağcı ◽  
Ömer Atış ◽  
Remzi Karadağ ◽  
Ali Akbaş ◽  
...  

2019 ◽  
pp. 18-23
Author(s):  
Ferreri F.M.B ◽  
Sapienza D

Background and Aim: Molecular epidemiology is an interdisciplinary field concerning the analysis of biological indicators and the investigation of individual DNA polymorphisms. The glutathione-S-transferases (GSTs) are one of the most studied metabolic gene families. They are involved in the genesis of oxidative stress and many authors hypothesize that some null polymorphic variants determine increasing toxic effects in tissues. Oxidative stress and antioxidant systems are very important in the onset and progress of glaucoma, one of the leading causes of blindness worldwide. We investigate the association of null variant of GST (M1 and T1) with the risk of primary open angle glaucoma (POAG) and we considered the ethical and legal implications of genetic procedures as a screening tool. Materials and Methods: We conducted a case-control study including 103 unrelated carriers of glaucoma in a southern Italian population (living in Eastern Sicily) and 150 unrelated healthy individuals as controls, whose buccal swabs samples were genotyped for GST polymorphisms using a standardized multiplex PCR based method. Results: In patients with glaucoma (primary open angle glaucoma, POAG) null genotype of the investigated genetic polymorphisms is very common compared to the healthy individuals. The obtained data suggest an influence of the (dual) null genotype on the normal metabolic pathway in the genesis of congenital glaucoma giving to these polymorphisms the role of so-called “indicators of susceptibility”. Conclusions: We conclude that the increased frequency of null GSTs (M1, T1) in patients with glaucoma could be considered a risk factor for incidence of the disease. Screenings can be carried out only in compliance with legislative rules. Keywords: Glaucoma; Glutathione S-transferase; GSTM1; GSTT1


2019 ◽  
Author(s):  
Ruyi Zhai ◽  
Huan Xu ◽  
Xinghuai Sun ◽  
Xiangmei Kong

Abstract Purpose: This study was aimed to analyze the profile of vascular and inflammatory cytokines in aqueous humor of primary open angle glaucoma (POAG) patients. Methods: Aqueous humor samples were acquired from 6 POAG patients and 7 age-related cataract patients that constituted the control group. A human cytokine antibody array was used to detect 37 proteins related to inflammation and vascular regulation. Characteristics including age, gender, and intraocular pressure (IOP) of POAG and age-related cataract patients were compared. Correlation analyses between aqueous humor cytokines and characteristics were performed. Results: The cytokine antibody array results showed that the signal intensities of soluble vascular endothelial growth factor receptor 1 (sVEGFR-1), von Willebrand factor (vWF), tumor necrosis factor (TNF)-α, and angiopoietin-2 in POAG patients were significantly higher in aqueous samples compared to controls (p < 0.05, Student’s test or Mann-Whitney U-test). Among cytokines of all aqueous samples, preoperative IOP was positively associated with expression quantity of sVEGFR-1 (r = 0.647, p = 0.02) and VEGF-A (r = 0.602, p = 0.04) and negatively associated with plasminogen activator inhibitor 1 expression (r = -0.593, p = 0.04). Values for sVEGFR-1 were positively correlated with vWF (r = 0.646, p = 0.02) and TNF-α (r = 0.824, p < 0.001) with statistical significance. Conclusion: Pathogenesis of primary open angle glaucoma may be associated with both vascular dysfunction and inflammatory responses. The vascular factors may include endothelial dysfunction and damaged vascular permeability as indicated by abnormal expression of vWF, sVEGFR-1 and angiopoietin-2. Keywords: POAG, aqueous humor, cytokines, sVEGFR-1, vWF, angiopoietin-2


Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1518 ◽  
Author(s):  
Jennifer A. Faralli ◽  
Mark S. Filla ◽  
Donna M. Peters

Primary open angle glaucoma (POAG) is the most common form of glaucoma and the 2nd most common cause of irreversible vision loss in the United States. Nearly 67 million people have the disease worldwide including >3 million in the United States. A major risk factor for POAG is an elevation in intraocular pressure (IOP). The increase in IOP is believed to be caused by an increase in the deposition of extracellular matrix proteins, in particular fibronectin, in a region of the eye known as the trabecular meshwork (TM). How fibronectin contributes to the increase in IOP is not well understood. The increased density of fibronectin fibrils is thought to increase IOP by altering the compliance of the trabecular meshwork. Recent studies, however, also suggest that the composition and organization of fibronectin fibrils would affect IOP by changing the cell-matrix signaling events that control the functional properties of the cells in the trabecular meshwork. In this article, we will discuss how changes in the properties of fibronectin and fibronectin fibrils could contribute to the regulation of IOP.


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